Background: Numerous proteins have been proposed as virulence factors for the gram negative gastric bacterium Helicobacter pylori but only for a few this has unequivocally been demonstrated. The aim of the current study was to evaluate the association of the putative virulence factors tnpA and tnpB (no cagA) with H. pylori associated gastroduodenal diseases. Methods: A PCR based assay was used to determine the presence of the tnpA and tnpB genes, as well as of cagA, in 360H. pylori strains isolated from H. pylori infected patients. Results: Of 360H. pylori culture positive patients (196 men, 164 women; average age 42.1 years (range 17–73), 95 had gastritis, 92 had gastric ulcers, 108 had duodenal ulcers, and 65 had gastric cancer. Using the gastritis group as a reference a significantly aberrant gene distribution was observed for the tnpA (Relative risk: 1.45; 95% CI 1.04-1.93), the cagA (Relative risk: 1.81; 95% CI 1.44-2.29), but not the tnpB gene in the gastric cancer group. Conclusions: The increased incidence of the tnpA gene in gastric cancer patients suggests a role of the tnpA gene in the development of H. pylori induced gastric cancer.